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Reprograming cancer cells by a BODIPY G-quadruplex stabiliser.

Aminesena Baser1, Beyza Basar2,3, Hanim Beyza Dogan1

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A novel cationic BODIPY stabiliser targets G-quadruplex DNA, significantly reducing cancer cell invasion and modulating metastasis-related genes. This G-quadruplex stabiliser shows promise for small molecule anti-cancer therapies.

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Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Cancer Research

Background:

  • G-quadruplex structures are increasingly recognized as potential therapeutic targets in cancer.
  • Developing selective small molecules to stabilize G-quadruplex DNA is a promising anti-cancer strategy.
  • Cancer cell migration and invasion are critical processes in metastasis that require modulation.

Purpose of the Study:

  • To develop and characterize a cationic BODIPY-based molecule with selective G-quadruplex stabilizing properties.
  • To evaluate the efficacy of the G-quadruplex stabilizer in inhibiting cancer cell migration and invasion.
  • To investigate the impact of the stabilizer on gene expression and cellular metabolism related to metastasis.

Main Methods:

  • Synthesis and characterization of a cationic BODIPY derivative.
  • G-quadruplex binding affinity and selectivity assays (e.g., using fluorescence spectroscopy).
  • In vitro assays to assess cancer cell migration and invasion.
  • Quantitative PCR (qPCR) to measure the expression of metastasis-related genes (HIF1α, VIM, CDH1).
  • Oxygen consumption rate measurements to analyze cellular metabolism.

Main Results:

  • A cationic BODIPY-based G-quadruplex stabilizer was successfully developed.
  • The stabilizer demonstrated significant inhibition of cancer cell migration and invasion (up to 90%).
  • Modulation of critical metastasis-associated genes (HIF1α, VIM, CDH1) was observed.
  • The compound reprogrammed hypoxia-adaptive metabolism, leading to a 1.82-fold increase in O2 consumption and restoration of normal energy metabolism.
  • Stabilizers with high G-quadruplex affinity (Kd = 0.38 μM) showed significant anti-cancer effects.

Conclusions:

  • Cationic BODIPY-based G-quadruplex stabilizers are effective in inhibiting cancer cell metastasis.
  • These stabilizers offer a novel approach to targeting cancer by modulating gene expression and cellular metabolism.
  • The developed G-quadruplex stabilizer represents a promising candidate for the development of small molecule anti-cancer drugs.